The research proposed in this application is for the development of a platform technology for the delivery of therapeutic genes to commensal bacteria associated with the human body. The successful development of the technology will result in the creation of a vehicle for the delivery of genes to bacteria inhabiting specific areas of the body, transforming the bacteria into localized therapeutic factories. The research objectives include the targeted delivery of nucleic acids encoding reporter genes, therapeutic proteins, or regulatory RNA to both Gram negative and Gram positive organisms. Proof of concept studies will demonstrate the flexibility and utility of the platform and the delivery of therapeutic immunomodulatory genes in vivo using a mouse model. The platform technology has the advantage of being adaptable, stable, and cost-effective and has broad application to human health including treatment of chronic disease conditions, immunotherapy, and vaccine development.